Blunted TSH responses to TRH administration in some depressed patients have been consistently observed by a number of different research groups. Data have also been reported suggesting a relationship between the magnitude of the TSH response and clinical course. It is unclear whether the blunted TSH response is more associated with state or trait-related factors. An alternative proposal for explaining the significance of the TSH response assessment in depression has been that the TSH response is actually of prognostic value with regard to long-term clinical course. We propose to extend previous studies conducted by other investigator and work carried out by our own group by examining the TRH stimulation test administered at 4 specific times within the context of a defined and highly-structured treatment protocol. Patients with major depressive disorder, endogenous subtype will be treated in a protocol involving the use of a 2 week placebo washout period, an active drug treatment phase with desipramine lasting for up to 24 weeks, and then a 10 week double-blind, placebo-control "crossover" phase. TRH testing will be performed at baseline and after 6 and 24 weeks of treatment with desipramine. A final TRH stimulation test will be conducted at the end of the 10 week crossover phase. The relationship between the TSH response to TRH and clinical state (as well as clinical course) will be examined in detail with this protocol. In addition, the response of peripheral thyroid hormones (T4, T3, reverse T3) will be studied after TRH administration to provide some index of possible alterations in thyroid axis responsiveness or metabolism at a more peripheral level. This proposal also calls for the evaluation of depressed patients who are undergoing cognitive theraphy and no medication treatment. These patients will be studies with TRH stimulation test while acutely depressed and after a 12 week course of cognitive therapy. This study should help to differentiate the effects of change in clinical state per se from the effects of desipramine on the TSH response to TRH. Finally, patients with anxiety disorders (generalized anxiety disorder and panic disorder) will be evaluated with the TRH stimulation test, as a relevant psychiatric comparison group for the studies with depressed patients.